1. Studies using positron emission tomography (PET) have reported that global and regional values for cerebral blood flow and metabolic rates for glucose decline with human aging. Using PET to measure brain glucose metabolism in healthy normotensive men of different ages, we determined that, whereas age-declines occurred in measurements uncorrected for atrophy, they were absent after atrophy correction. This argues that healthy human aging is not accompanied by reduced brain glucose metabolism, a marker of local functional activity. (Ibanez et al 2004) 2. We reviewed functional imaging and postmortem data to conclude that brain failure in Alzheimer disease occurs in two stages. The first stage is associated with reduced synaptic efficacy and reduced glucose metabolism, and is potentially reversible. The second stage, in moderate-severe dementia, is associated with neurofibrillary tangle formation, cell death and synaptic dropout, and is irreversible. The brain can be almost normally activated in the first but not the second stage. (Rapoport 2005a) (Rapoport 2005b).